Project Summary ? Bioanalytical Core The Bioanalytical Core Laboratory will provide state of the art and innovative bioanalytical expertise and techniques for the quantification of drugs and their metabolites, endogenous chemicals and other molecules of biological significance in new collaborative studies with the other cores in the center and all the funded drug abuse biomedical researchers at this and neighboring universities. These analyses will provide the expertise to perform new and innovative research and to enhance currently funded research projects in ways not anticipated at the time of their application submission. This core will accomplish these goals by making available reliable, validated mass spectrometric analysis of biological and non-biological materials for new projects as well as for NIH sponsored and other researchers studying the mechanism of action of abused substances and addiction. The laboratory will develop methods focused on the identification and quantification in biologic specimens of drugs and/or drug metabolites, such as cocaine, nicotine, cotinine, tetrahydrocannabinol (THC), and, natural occurring psychoactive compounds such as nuciferine, apomorphine and mitragynine, as well as physiologically active small endogenous molecules and/or their metabolites such as anandamide, other endocannabinoids, prostamides and ceramide metabolites of sphingomelingolipids. These analyses will enhance the pharmacological studies of drugs of abuse by providing pharmacokinetic analysis including drug disposition, metabolism and clearance. The Bioanalytical Core will develop novel and innovative techniques for minimum sample preparation to allow rapid isolation and quantification of polar drug metabolites and glucuronide metabolites. We will expand on the breadth of types of small molecules including additional substances of abuse designer drugs (i.e., synthetic opioids, cannabimimetic, and cathinones), and their metabolites, a wider range of endogenous compounds which have similar pharmacological effects as drugs of abuse including endocannabinoids, peptides, lipids and other biological transmitters or signaling compounds. We will also enhance selectivity capabilities with differential ion mobility mass spectrometry (DMS) allowing us to increase our quantification of isobaric compounds, identify metabolites not seen before, and separation of ions of interest from interfering ions. Incorporating micro-extraction/sample preparation technologies and/or two-dimensional chromatographic separations combined with mass spectrometry (MS), DMS selectivity capability, will provide new dimensions to the research proposed of all drug abuse researchers on this campus and those in our neighboring institutions.